Approximately 17 million Americans take nonsteroidal anti-inflammatory drugs (NSAIDS) daily for treatment of pain or inflammation. These drugs are nonselective inhibitors of the enzymes cyclooxygenase (COX) 1 and 2, which convert arachidonic acid to prostaglandins. Two COX-2 inhibitors, celecoxib and rofecoxib, were introduced in 1999 in the biggest drug launch ever. To date, more than 6.6 million prescriptions have been filled. A third drug, meloxicam, which was recently introduced in the United States, has a high affinity for COX-2 but also inhibits COX-1 at therapeutic doses. However, several of these COX-2 inhibitors have been recalled due to their side effects of increasing adverse cardiovascular events. Thus, there remains a need for COX-2 inhibitors that can be administered such that the adverse cardiovascular effects are avoided.
There is a great deal of evidence that inhibitors of COX-2 are useful in treating colon cancer and inflammatory diseases of the colon. For example, it has been observed that inhibitors of COX-2 sensitize colon cancer cells to a form of apoptosis called TRAIL-induced apoptosis (Martin et al., 2005, Cancer Research 65:11447-11458). Further, results presented at the American Society of Clinical Oncology 2005 Annual Meeting showed that patients with stage ITT colon cancer may benefit from aspirin as much as from surgery and standard chemotherapy alone. The study also found a similar result for COX-2 inhibitors celecoxib (CELEBREX®) and rofecoxib (VIOXX®). Moreover, the COX-2 inhibitor celecoxib (CELEBREX®) has been demonstrated to reduce the number of colon polyps in patients with Familial Adenomatous Polyposis (FAP). Patients with FAP develop hundreds to thousands of precancerous polyps (adenomas) throughout the colon and rectum. Left untreated, nearly all FAP patients develop colorectal cancer by their 40s and 50s. The primary treatment for FAP is surgical removal of most or all of the colon and rectum with subsequent surveillance of any remaining colorectal segment. Based on NIH-sponsored clinical results, the FDA approved celecoxib (CELEBREX®) as an adjunctive drug (an accessory or auxiliary agent) that could be added to the standard of care in people with FAP. There is a need in the art to develop COX-2 inhibitors that remain active in the digestive tract and are not systemically absorbed.
U.S. Pat. Nos. 5,211,944 and 5,494,661 to Tempesta disclose the use of a proanthocyanidin polymeric composition isolated from Croton spp. or Calophyllum spp. for the treatment of viral infections. Rozhon et al., U.S. Patent Publication No. 2005/0019389, disclose the use of a proanthocyanidin polymeric composition isolated from Croton spp. or Calophyllum spp. for the treatment of secretory or traveler's diarrhea.
Citation or identification of any reference in this section or any other section of this application shall not be construed as an admission that such reference is available as prior art for the present application.